{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:44:05Z","timestamp":1791776645823,"version":"4.3.4"},"posted":{"date-parts":[[2026,9,9]]},"group-title":"Microbiology","reference-count":78,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["PJT-206152"],"award-info":[{"award-number":["PJT-206152"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DE031274"],"award-info":[{"award-number":["DE031274"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Saint Louis University President\u2019s Research Fund"},{"name":"University of Washington\u2019s Proteomics Resource","award":["UWPR95794"],"award-info":[{"award-number":["UWPR95794"]}]},{"name":"Canada Graduate Scholarship \u2013 Doctoral and a Michael Smith Foreign Study Supplement from the Natural Sciences and Engineering Research Council of Canada"},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"John F. Enders Professorship in Microbial Pathogenesis at Yale University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Bacteria contend with a wide range of antagonistic interactions from neighboring microbes. One widespread but poorly understood threat is posed by Patescibacteria, which proliferate by colonizing host bacteria surfaces and extracting cellular resources. Despite the ubiquity of Patescibacteria in the environment, how hosts defend against these epibionts remains unknown. Here we show that Actinomycetota fend off Patescibacteria using the Esx secretion system. We identify a secreted effector protein that mediates this defensive behavior and demonstrate that Esx induction is part of a multifaceted, epibiont-specific response that includes multiple predicted cell surface modifications. Finally, we show that this response occurs at the transcriptional level and is mediated by a previously undescribed threat sensing pathway whose activation leads to threonine phosphorylation of an FHA domain-containing output protein. Together with bioinformatic evidence linking this threat sensing pathway to Esx across Actinomycetales, our experimental findings establish a functional role for the elusive and broadly distributed Esx pathway in defense against epibionts. Furthermore, they help resolve the ecological relationship between Patescibacteria and their hosts as one of antagonism, not mutualism.<\/jats:p>","DOI":"10.64898\/2026.09.08.750141","type":"posted-content","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:30:21Z","timestamp":1789011021000},"source":"Crossref","is-referenced-by-count":1,"title":["Oral Actinobacteria sense and defend against parasitic epibionts"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3278-6127","authenticated-orcid":false,"given":"Yaxi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-0999","authenticated-orcid":false,"given":"Jake","family":"Colautti","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"},{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada"},{"name":"Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1517-4236","authenticated-orcid":false,"given":"Larry A.","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2361-1498","authenticated-orcid":false,"given":"Yongjun","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Louis University, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Farrell","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1797-1730","authenticated-orcid":false,"given":"Batbileg","family":"Bor","sequence":"additional","affiliation":[{"name":"Department of Microbiology, ADA Forsyth Institute, Somerville MA, 02143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-8836","authenticated-orcid":false,"given":"John C.","family":"Whitney","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada"},{"name":"Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada"},{"name":"David Braley Center for Antibiotic Discovery, McMaster University, Hamilton, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8535-7620","authenticated-orcid":false,"given":"Dapeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biology, Saint Louis University, St. Louis, MO, USA"},{"name":"Program of Bioinformatics and Computational Biology, Saint Louis University, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2648-0965","authenticated-orcid":false,"given":"S. Brook","family":"Peterson","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-4861","authenticated-orcid":false,"given":"Joseph D.","family":"Mougous","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University, New Haven, CT, USA"},{"name":"Howard Hughes Medical Institute, Yale University, New Haven, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091107000662000_2026.09.08.750141v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01017-1"},{"key":"2026091107000662000_2026.09.08.750141v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.06.103"},{"key":"2026091107000662000_2026.09.08.750141v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-023-00934-x"},{"key":"2026091107000662000_2026.09.08.750141v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2023.102312"},{"key":"2026091107000662000_2026.09.08.750141v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2025.07.016"},{"key":"2026091107000662000_2026.09.08.750141v1.6","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05701"},{"key":"2026091107000662000_2026.09.08.750141v1.7","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74658"},{"key":"2026091107000662000_2026.09.08.750141v1.8","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.000789"},{"key":"2026091107000662000_2026.09.08.750141v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-023-01401-4"},{"key":"2026091107000662000_2026.09.08.750141v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0672-6"},{"key":"2026091107000662000_2026.09.08.750141v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2020.09.001"},{"key":"2026091107000662000_2026.09.08.750141v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1708-z"},{"key":"2026091107000662000_2026.09.08.750141v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1808469115"},{"key":"2026091107000662000_2026.09.08.750141v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09204-7"},{"key":"2026091107000662000_2026.09.08.750141v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2023.12.024"},{"key":"2026091107000662000_2026.09.08.750141v1.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2419369121"},{"key":"2026091107000662000_2026.09.08.750141v1.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1419038112"},{"key":"2026091107000662000_2026.09.08.750141v1.18","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01711-22"},{"key":"2026091107000662000_2026.09.08.750141v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22762-4"},{"key":"2026091107000662000_2026.09.08.750141v1.20","doi-asserted-by":"publisher","DOI":"10.1099\/ijsem.0.006668"},{"key":"2026091107000662000_2026.09.08.750141v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.15823"},{"key":"2026091107000662000_2026.09.08.750141v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114909119"},{"key":"2026091107000662000_2026.09.08.750141v1.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2319790121"},{"key":"2026091107000662000_2026.09.08.750141v1.24","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01488-21"},{"key":"2026091107000662000_2026.09.08.750141v1.25","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00560-5"},{"key":"2026091107000662000_2026.09.08.750141v1.26","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-012420-081657"},{"key":"2026091107000662000_2026.09.08.750141v1.27","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.13971"},{"key":"2026091107000662000_2026.09.08.750141v1.28","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001420"},{"key":"2026091107000662000_2026.09.08.750141v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2016.183"},{"key":"2026091107000662000_2026.09.08.750141v1.30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009204"},{"key":"2026091107000662000_2026.09.08.750141v1.31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.26938"},{"key":"2026091107000662000_2026.09.08.750141v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-026-74429-7"},{"key":"2026091107000662000_2026.09.08.750141v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.03.040"},{"key":"2026091107000662000_2026.09.08.750141v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2026.113240"},{"key":"2026091107000662000_2026.09.08.750141v1.35","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2312455121"},{"key":"2026091107000662000_2026.09.08.750141v1.36","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.802645"},{"key":"2026091107000662000_2026.09.08.750141v1.37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1409345111"},{"key":"2026091107000662000_2026.09.08.750141v1.38","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12770"},{"key":"2026091107000662000_2026.09.08.750141v1.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602606103"},{"key":"2026091107000662000_2026.09.08.750141v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2015.01.002"},{"key":"2026091107000662000_2026.09.08.750141v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2022.152321"},{"key":"2026091107000662000_2026.09.08.750141v1.42","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.70368"},{"key":"2026091107000662000_2026.09.08.750141v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-023-00673-0"},{"key":"2026091107000662000_2026.09.08.750141v1.44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1012028"},{"key":"2026091107000662000_2026.09.08.750141v1.45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.46883"},{"key":"2026091107000662000_2026.09.08.750141v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2021.06.017"},{"key":"2026091107000662000_2026.09.08.750141v1.47","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52696"},{"key":"2026091107000662000_2026.09.08.750141v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-011-1018-1"},{"key":"2026091107000662000_2026.09.08.750141v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2016.12.003"},{"key":"2026091107000662000_2026.09.08.750141v1.50","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520905792"},{"key":"2026091107000662000_2026.09.08.750141v1.51","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0260-6"},{"key":"2026091107000662000_2026.09.08.750141v1.52","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2215990119"},{"key":"2026091107000662000_2026.09.08.750141v1.53","doi-asserted-by":"publisher","DOI":"10.1038\/s41559-023-02230-6"},{"key":"2026091107000662000_2026.09.08.750141v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102318"},{"key":"2026091107000662000_2026.09.08.750141v1.55","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00134-22"},{"key":"2026091107000662000_2026.09.08.750141v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1318"},{"key":"2026091107000662000_2026.09.08.750141v1.57","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00811-10"},{"key":"2026091107000662000_2026.09.08.750141v1.58","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02049"},{"key":"2026091107000662000_2026.09.08.750141v1.59","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.13.4173-4176.1994"},{"key":"2026091107000662000_2026.09.08.750141v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.08.017"},{"key":"2026091107000662000_2026.09.08.750141v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0201-4"},{"key":"2026091107000662000_2026.09.08.750141v1.62","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026091107000662000_2026.09.08.750141v1.63","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"2026091107000662000_2026.09.08.750141v1.64","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.261"},{"key":"2026091107000662000_2026.09.08.750141v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2016.136"},{"key":"2026091107000662000_2026.09.08.750141v1.66","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"2026091107000662000_2026.09.08.750141v1.67","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"2026091107000662000_2026.09.08.750141v1.68","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01773-0"},{"key":"2026091107000662000_2026.09.08.750141v1.69","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"2026091107000662000_2026.09.08.750141v1.70","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340"},{"key":"2026091107000662000_2026.09.08.750141v1.71","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu033"},{"key":"2026091107000662000_2026.09.08.750141v1.72","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab408"},{"key":"2026091107000662000_2026.09.08.750141v1.73","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1135"},{"key":"2026091107000662000_2026.09.08.750141v1.74","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002195"},{"key":"2026091107000662000_2026.09.08.750141v1.75","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa913"},{"key":"2026091107000662000_2026.09.08.750141v1.76","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.03.016"},{"key":"2026091107000662000_2026.09.08.750141v1.77","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab776"},{"key":"2026091107000662000_2026.09.08.750141v1.78","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00985-13"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.08.750141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T14:00:12Z","timestamp":1789135212000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.08.750141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":78,"URL":"https:\/\/doi.org\/10.64898\/2026.09.08.750141","relation":{},"subject":[],"published":{"date-parts":[[2026,9,9]]},"subtype":"preprint"}}